Researchers from institutions in Cleveland have discovered an unexpected molecular mechanism that controls fat formation in the body, and deactivating it produced remarkable outcomes.
Worldwide, obesity and fatty liver disease are surging in prevalence due to increasingly calorie-rich diets and increasingly inactive lifestyles.
A team of scientists based in Cleveland pinpointed a novel enzyme required by the body for fat synthesis.
By inhibiting this enzyme, the researchers halted weight increase and lowered harmful cholesterol concentrations.
This breakthrough is now fueling the creation of a promising multi-target medication designed to combat obesity, fatty liver disease, and cardiovascular conditions simultaneously.
Global Surge in Obesity and Fatty Liver Conditions
Obesity represents a major worldwide health emergency, serving as a primary driver of numerous diseases and premature mortality. It significantly elevates the chances of developing severe ailments like cardiovascular disease and metabolic dysfunction-associated steatotic liver disease, commonly known as MASLD. With dietary patterns evolving to favor high-calorie processed foods and physical activity diminishing in everyday routines, the incidence of these health issues has risen progressively across the globe.
Nitric oxide, a naturally occurring gas within the human body, plays a pivotal role in regulating various physiological functions. It exerts its effects by binding to specific proteins, thereby modulating their activity. Striking the proper equilibrium in nitric oxide levels is vital for health. Imbalances, such as excessive or insufficient binding to critical proteins, can pave the way for pathological conditions.
Discovery of a Key Enzyme Activating Fat Synthesis
In a groundbreaking study featured in Science Signaling, a collaborative team from University Hospitals and Case Western Reserve University unveiled SCoR2, an enzyme previously unrecognized by science. This enzyme functions by stripping nitric oxide away from proteins involved in controlling fat accumulation. The removal of nitric oxide triggered the activation of fat production pathways, underscoring SCoR2’s indispensable role in the fat-making process.
Inhibiting the Enzyme Halts Weight Gain in Animal Studies
Building on their findings, the research group explored the consequences of suppressing SCoR2 activity. They employed both genetic engineering techniques and a custom-developed pharmacological inhibitor to achieve this blockade. In experimental mouse models, disabling SCoR2 completely prevented weight accumulation and shielded the liver from damage. Furthermore, the intervention successfully diminished circulating levels of detrimental cholesterol.
“We now possess an entirely new category of therapeutic agents that not only prevent weight gain but also reduce cholesterol levels—a promising treatment option for obesity and heart disease, complete with supplementary advantages for liver function,” stated Jonathan Stamler, MD, the study’s principal investigator. Dr. Stamler holds prestigious positions including President and Co-Founder of the Harrington Discovery Institute, Distinguished University Professor, the Robert S. and Sylvia K. Reitman Family Foundation Professor of Cardiovascular Innovation, and Professor of Medicine and Biochemistry at both University Hospitals and Case Western Reserve University.
Mechanisms of Nitric Oxide in Controlling Fat and Cholesterol
According to Dr. Stamler, nitric oxide serves as an innate inhibitor of fat synthesis across multiple tissue types. “Within the liver, nitric oxide suppresses the activity of proteins responsible for producing fat and cholesterol. In adipose tissue, it blocks the genetic mechanisms that drive the expression of fat-synthesizing enzymes,” he elaborated.
The research team is gearing up to advance their inhibitory drug into human clinical trials, a transition anticipated to require approximately 18 months of preparatory work.
“Our group is eager to progress this pioneering drug candidate, which blocks weight gain, decreases cholesterol, and promotes liver wellness,” Dr. Stamler affirmed.
Backing for Drug Advancement and Wider Implications
Further progression of this drug will receive backing from the Harrington Discovery Institute at University Hospitals, a dedicated entity that transforms innovative scientific discoveries into viable therapies for pressing unmet medical challenges. Celebrating its 13th year of operation, the institute boasts an impressive track record: 227 medicines under development, support extended to 75 institutions, the launch of 46 companies, 24 medicines advancing through clinical trials, and 15 licensing agreements with pharmaceutical giants.
